vitamin-a2 and Abnormalities--Drug-Induced

This study demonstrates early embryonic metabolism of exogenous all-trans-3,4-didehydroretinol (vitamin A2) to all-trans-3,4-didehydroretinal and to all-trans-3,4-didehydroretinoic acid in Xenopus embryos during neurulation. The latter metabolite was recently shown to bind with high affinity and to activate various retinoic acid receptors. Embryos treated with all-trans-3,4-didehydroretinol during early or late gastrulation exhibited abnormalities along the anteroposterior axis. The abnormalities were primarily in the posterior regions of the embryo, with only minor defects anteriorally. Eye malformations, typical for early exposure to 9-cis- and all-trans-retinols and retinals (companion paper), were not observed. We also present evidence that all-trans-3,4-didehydroretinoic acid is present endogenously during early neurulation and is evenly distributed along the anteroposterior axis. After treatment with all-trans-3,4-didehydroretinol, embryonic levels of all-trans-3,4-didehydroretinoic acid exceeded endogenous levels of this metabolite during early and late neurulation. We hypothesize that the dysmorphogenic effects produced by treatment of Xenopus embryos with the alcohol precursor, all-trans-3,4-didehydroretinol, are the result of its embryonic conversion to its corresponding acid ligand.

Topics: Abnormalities, Drug-Induced; Animals; Chromatography, High Pressure Liquid; Embryo, Nonmammalian; Female; Phenotype; Teratogens; Tretinoin; Vitamin A; Xenopus laevis